Transient increases in p53-responsible gene expression at early stages of Epstein-Barr virus productive replication

Yoshitaka Sato, Noriko Shirata, Takayuki Murata, Sho Nakasu, Ayumi Kudoh, Satoko Iwahori, Sanae Nakayama, Shigeki Chiba, Hiroki Isomura, Teru Kanda, Tatsuya Tsurumi

研究成果: Article査読

23 被引用数 (Scopus)

抄録

Expression of Epstein-Barr Virus BZLF1, a key protein initiating the switch from latent to lytic infection, is known to cause cell growth arrest by accumulating p53 and p21WAF1/CIp1 in epithelial cells, but its molecular mechanism remains elusive. We found here that the BZLF1 protein stimulates p53 binding to its recognition sequence. the BZLF1 accelerated the rate of p53-DNA complex formation through the interaction with p53 protein and also enhanced p53-specific transcription in vitro. Furthermore, p53 protein was found to bind to its target promoter regions specifically in the early stages of lytic replication. overexpression of p53 at the early stages of lytic replication enhanced viral genome replication, supporting the idea that p53 plays an important role in the initiation steps of eBV replication. taking the independent role of BZLF1 on p53 degradation into consideration, we propose that the BZLF1 protein regulates p53 and its target gene products in two distinctive manners; transient induction of p53 at the early stages for the initiation of viral productive replication and p53 degradation at the later stages for S-phase like environment preferable for viral replication.

本文言語English
ページ(範囲)807-814
ページ数8
ジャーナルCell Cycle
9
4
DOI
出版ステータスPublished - 15-02-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学
  • 細胞生物学

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